Dataset Information

KRASG12D and TP53R167H Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs.

ABSTRACT: Although survival has improved in recent years, the prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poor. Despite substantial differences in anatomy, physiology, genetics, and metabolism, the overwhelming majority of preclinical testing relies on transgenic mice. Hence, while mice have allowed for tremendous advances in cancer biology, they have been a poor predictor of drug performance/toxicity in the clinic. Given the greater similarity of sus scrofa pigs to humans, we engineered transgenic sus scrofa expressing a LSL-KRASG12D-TP53R167H cassette. By applying Adeno-Cre to pancreatic duct cells in vitro, cells self-immortalized and established tumors in immunocompromised mice. When Adeno-Cre was administered to the main pancreatic duct in vivo, pigs developed extensive PDAC at the injection site hallmarked by excessive proliferation and desmoplastic stroma. This serves as the first large animal model of pancreatic carcinogenesis, and may allow for insight into new avenues of translational research not before possible in rodents.

SUBMITTER: Principe DR

PROVIDER: S-EPMC6105629 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

KRAS<sup>G12D</sup> and TP53<sup>R167H</sup> Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs.

Principe Daniel R DR Overgaard Nana Haahr NH Park Alex J AJ Diaz Andrew M AM Torres Carolina C McKinney Ronald R Dorman Matthew J MJ Castellanos Karla K Schwind Regina R Dawson David W DW Rana Ajay A Maker Ajay A Munshi Hidayatullah G HG Rund Lauretta A LA Grippo Paul J PJ Schook Lawrence B LB

Scientific reports 20180822 1

Although survival has improved in recent years, the prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poor. Despite substantial differences in anatomy, physiology, genetics, and metabolism, the overwhelming majority of preclinical testing relies on transgenic mice. Hence, while mice have allowed for tremendous advances in cancer biology, they have been a poor predictor of drug performance/toxicity in the clinic. Given the greater similarity of sus scrofa pigs to ...[more]

PMID: 30135483

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Project description:BackgroundIn recent years, the wildlife/livestock interface has attracted increased attention due to disease transmission between wild and domestic animal populations. The ongoing spread of African swine fever (ASF) in European wild boar (Sus scrofa) emphasize the need for further understanding of the wildlife/livestock interface to prevent disease spill-over between the wild and domestic populations. Although wild boar may also act as a potential source for other infectious disease agents, ASF is currently the most severe threat from wild boar to domestic pigs. To gather information on the wild boar situation at commercial pig producing farms in Sweden, a digital questionnaire survey was distributed through the animal health services.ResultsMost pigs produced for commercial purposes in Sweden are raised without outdoor access. Of the 211 responding pig producers, 80% saw wild boar or signs of wild boar activity in the vicinity of their farm at least once during the year. Observations were significantly correlated with geographical region, but there was no correlation between farm characteristics (farm size, main type of production, outdoor access) and observed wild boar presence or proximity. However, a reported higher frequency of wild boar observations was positively correlated with the observations being made in closer proximity to the farm. Hunting and strategic baiting were the most common mitigation strategies used to keep wild boar at bay. Of the 14 farms raising pigs with outdoor access, 12 responded that these pigs could be raised solely indoors if needed. Pigs with outdoor access are required to be fenced in, but double fencing in these outdoor pig enclosures was not practiced by all. A perimeter fence surrounding any type of pig farm was very rare. More than half of the producers that grew crops with intended use for pigs reported crop damage by wild boar.ConclusionThis study shows that although pigs raised for commercial purposes in Sweden are, to a large extent, kept indoors the potential for indirect contact with wild boar exists and must be considered. Variable local situations regarding wild boar abundance may require an adaptive approach regarding biosecurity efforts.

Dataset Information

KRASG12D and TP53R167H Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs.

Publications

KRAS<sup>G12D</sup> and TP53<sup>R167H</sup> Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs.

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